WEBVTT - One Drug's Journey 0:00:04.760 --> 0:00:08.080 Millions of Americans take prescription drugs, but how many of 0:00:08.160 --> 0:00:11.039 us really know how they were developed or how they 0:00:11.039 --> 0:00:15.280 even work. For most of us, drugs are just there 0:00:15.800 --> 0:00:18.479 when you pick up your prescription from the pharmacy. You 0:00:18.520 --> 0:00:20.599 don't think about the billions of dollars that went into 0:00:20.640 --> 0:00:25.160 the research or the scientific breakthroughs that paved the way. 0:00:26.840 --> 0:00:31.120 Welcome to Prognosis, a podcast about health, medical technology, and 0:00:31.160 --> 0:00:34.640 the mind blowing innovation that's underway across the globe. I'm 0:00:34.640 --> 0:00:38.760 your host, Michelle fay Cortez. This week, we're hearing the 0:00:38.800 --> 0:00:41.839 story of the strange, circuitous path of one drug from 0:00:41.840 --> 0:00:45.280 the Eureka moment to the market. It's a story about 0:00:45.320 --> 0:00:49.440 a Nobel Prize winner, cutting edge genetic research, billions of 0:00:49.440 --> 0:01:00.520 pharmaceutical dollars, and of all things, a worm. In August, 0:01:00.560 --> 0:01:05.000 all Nylum, a seven billion dollar biotechnology company, one approval 0:01:05.040 --> 0:01:07.800 to market its first drug. The company hopes it will 0:01:07.800 --> 0:01:10.759 save the lives of roughly fifty patients who suffer from 0:01:10.760 --> 0:01:16.840 a rare and ultimately fatal disorder. But the price sounds outrageous. 0:01:19.160 --> 0:01:22.960 Beach patient, or rather the federal government and their insurance companies, 0:01:23.240 --> 0:01:26.040 will have to pay about three forty five thousand dollars 0:01:26.080 --> 0:01:30.640 every year. Here's Rebecca's Balding, Bloomberg's Boston Biotech Reporter on 0:01:30.680 --> 0:01:45.200 the sixteen year journey of a single drug. I'm here 0:01:45.240 --> 0:01:48.840 in Cambridge, Massachusetts, the global capital of the drug industry. 0:01:49.520 --> 0:01:52.640 As a pharmaceutical executive told me recently, what New York 0:01:52.720 --> 0:01:55.920 is to finance and Paris is to culture, Cambridge is 0:01:55.960 --> 0:01:59.600 to science. Its heart is a place called Kendall Square, 0:01:59.680 --> 0:02:02.480 next at M. I. T. Kendall Square used to be 0:02:02.560 --> 0:02:06.640 a rundown neighborhood full of empty candy factories. Now the 0:02:06.640 --> 0:02:09.600 neighborhood is full of gleaming buildings and companies with names 0:02:09.600 --> 0:02:16.200 that suggest scientific expertise and mystery genzyme biogen voyager. Their 0:02:16.200 --> 0:02:19.760 market values are usually counted by the billions. When you're 0:02:19.760 --> 0:02:22.000 walking around the streets, you get the feeling that people 0:02:22.080 --> 0:02:25.200 hidden behind glass walls are making decisions about the future, 0:02:25.960 --> 0:02:30.000 possibly your future. Al Nylum is one of those companies. 0:02:31.639 --> 0:02:34.680 All Nylum is named after the center star in Orion's belt, 0:02:34.800 --> 0:02:38.880 the brightest in the constellation. It's a fitting metaphor. Al 0:02:38.960 --> 0:02:44.240 Nylum is the platonic ideal of a biotech company. Sixteen 0:02:44.320 --> 0:02:46.840 years ago, a group of scientists here wanted to take 0:02:46.880 --> 0:02:50.120 an obscure insight about genetics and turn it into a drug. 0:02:50.960 --> 0:02:53.919 This is the story about that drug, but it's also 0:02:53.960 --> 0:02:57.079 a story about the biotech industry itself and what happens 0:02:57.120 --> 0:03:00.399 behind those glass walls and it all be I'm back 0:03:00.400 --> 0:03:02.920 in the late seventies when a story in the Washington 0:03:03.000 --> 0:03:05.560 Post piqued the interest of a high school student named 0:03:05.600 --> 0:03:10.400 Craig Mellow. Today, Craig is fifty eight years old. I 0:03:10.440 --> 0:03:12.840 spoke to him on the campus of the Massachusetts Medical 0:03:12.880 --> 0:03:16.360 Center in Worcester, where he runs a genetics lab. I 0:03:16.440 --> 0:03:19.400 don't really know what to call Craig. My producers tell 0:03:19.440 --> 0:03:22.320 me first names worked better for podcasts, But the reality 0:03:22.400 --> 0:03:25.920 is Craig has a Nobel Prize. But Dr Mellow doesn't 0:03:25.960 --> 0:03:29.600 sound right either. Craig is tall and athletic, with long 0:03:29.639 --> 0:03:32.320 gray hair. I would pay him more as an enlightened 0:03:32.320 --> 0:03:37.040 surfer pondering the universe than a celebrated molecular biologist. Here's 0:03:37.040 --> 0:03:41.400 what started his interest in genetics. I got really fascinated 0:03:41.480 --> 0:03:45.480 by genetics when I learned that the human insulin gene 0:03:45.920 --> 0:03:50.440 could be expressed in bacteria that you could actually take 0:03:50.480 --> 0:03:53.520 the human gene for insulin, put it into bacteria, and 0:03:53.520 --> 0:03:56.520 the bacteria could make the human insulin protein. And I 0:03:56.560 --> 0:03:59.600 read that in the Washington Post and I said, you know, 0:03:59.640 --> 0:04:04.160 that's been to myself. That's incredibly powerful. Most people didn't 0:04:04.200 --> 0:04:07.480 know it yet, but that discovery was the biotechnology industry's 0:04:07.600 --> 0:04:14.480 big bang, the moment that would change medicine forever. Researchers 0:04:14.520 --> 0:04:17.839 had shown that could make insulin a human hormone in 0:04:17.920 --> 0:04:21.880 a lab. Here's why that's such a big deal. Most 0:04:21.920 --> 0:04:25.719 medicines before then had been simple chemicals. Truth be told, 0:04:25.760 --> 0:04:29.239 many of them didn't even work that well. Synthetic insulin 0:04:29.320 --> 0:04:31.960 was one of the first medicines made from human cells, 0:04:32.520 --> 0:04:36.200 and it worked beautifully. Diabetics who had previously relied on 0:04:36.279 --> 0:04:39.640 insulin made from pigs and cattle finally had the real thing. 0:04:40.720 --> 0:04:42.919 It was also an innovation that made Craig want to 0:04:42.920 --> 0:04:46.800 go into medical research. Yeah. I always was interested in 0:04:46.880 --> 0:04:50.680 the history of life and fossils, but the genetic information 0:04:50.760 --> 0:04:55.520 inside of every cell in our bodies is a living fossil, 0:04:55.839 --> 0:04:59.880 I'd say. I was so intrigued by the fundamental quest 0:05:00.000 --> 0:05:03.640 gens of origins, even if it weren't applicable to anything. 0:05:04.080 --> 0:05:06.680 I think it would be really fascinating and important to 0:05:06.720 --> 0:05:09.760 try to understand this. But of course it turns out 0:05:09.839 --> 0:05:14.599 that by understanding fundamental mechanisms of of biology, we can 0:05:14.640 --> 0:05:19.000 make really important medicines like insulin. Craig decided to study 0:05:19.120 --> 0:05:22.040 DNA specifically how he might be able to tinker with it. 0:05:22.600 --> 0:05:25.839 Put simply, DNA as our body's blueprint, the master code 0:05:25.839 --> 0:05:28.880 that lays out all of its processes. But it's just 0:05:29.160 --> 0:05:32.400 the blueprint. To actually create life, you need a builder 0:05:32.440 --> 0:05:36.800 and raw materials too. That's where a molecule called ribonucleic 0:05:36.880 --> 0:05:40.880 acid or RNA comes in. If you're wondering what any 0:05:40.960 --> 0:05:43.640 of this has to do with developing a drug, specifically 0:05:43.680 --> 0:05:47.520 al Nylums drug, stick with me. But first let's go 0:05:47.560 --> 0:05:51.680 over some basic molecular biology. It's really simple, I promise. 0:05:52.640 --> 0:05:56.120 If DNA is the blueprint, RNA is the contractor that 0:05:56.160 --> 0:05:59.480 gets hired to actually build the building. It reads the 0:05:59.600 --> 0:06:03.480 architect plans and carries them out. In this scenario, Proteins 0:06:03.480 --> 0:06:06.440 are the equivalence of brick or drywall. Proteins are what 0:06:06.480 --> 0:06:08.600 the body is actually made up of. They make up 0:06:08.640 --> 0:06:12.760 your hair, your eyes, your heart, every cell. RNA is 0:06:12.800 --> 0:06:15.640 what creates them by reading the DNA's code and turning 0:06:15.640 --> 0:06:19.320 that code into proteins. Most of the time this goes well, 0:06:19.640 --> 0:06:22.800 except when there's an air in the blueprint. Defective DNA 0:06:23.080 --> 0:06:27.560 turns into defective proteins, which in turn caused disease. And 0:06:27.560 --> 0:06:30.680 in all of these cases, even though DNA has an error, 0:06:30.760 --> 0:06:35.680 the RNA still repeats it. An error in one protein 0:06:35.800 --> 0:06:39.320 may sound benign, but it's not. It's what causes disease. 0:06:39.800 --> 0:06:43.080 That's why tinkering with DNA was so allerting for researchers. 0:06:43.520 --> 0:06:46.320 If scientists like Craig could figure out how to change 0:06:46.360 --> 0:06:49.880 the blueprint, they could prevent disease. That's key for later 0:06:49.920 --> 0:06:51.960 on in the episode when we'll hear about how this 0:06:52.040 --> 0:06:55.560 drug was actually developed. But back when Craig was first tinkering, 0:06:56.000 --> 0:06:58.279 he was about as far as you could be from 0:06:58.279 --> 0:07:02.679 developing a drug for human beings. For his experiments, Craig 0:07:02.720 --> 0:07:10.080 worked on worms, yes, worms, specifically a species known as C. Elegants. 0:07:10.120 --> 0:07:13.480 It's a favorite creature among genetic researchers because it's so simple. 0:07:14.040 --> 0:07:16.840 It only has about a thousand cells humans have thirty 0:07:16.880 --> 0:07:21.480 seven trillion. It's tiny only about one millimeter long and transparent. 0:07:21.920 --> 0:07:25.080 You can see through all those cells under microscope. Despite 0:07:25.080 --> 0:07:28.400 its small size, it has a nervous system. That's key. 0:07:28.600 --> 0:07:31.080 The hope is that discoveries made on these animals might 0:07:31.160 --> 0:07:34.480 also work in people. Craig had always been interested in 0:07:34.560 --> 0:07:38.200 changes in DNA, but when he started his scientific career 0:07:38.240 --> 0:07:43.120 after grad school, something surprising happened. Other researchers around the 0:07:43.120 --> 0:07:47.840 country were experimenting not on DNA but on RNA. They 0:07:47.840 --> 0:07:52.440 were getting strange, even inexplicable results. Craig decided to try 0:07:52.480 --> 0:07:58.320 it for himself. I discovered some really weird things were happening, 0:07:58.680 --> 0:08:03.240 really really awful, but weird. When Craig injected his worms 0:08:03.240 --> 0:08:05.760 with DNA, he would have to inject them into the 0:08:05.800 --> 0:08:09.560 worm's reproductive organs. Genetic changes would then appear in the 0:08:09.560 --> 0:08:13.280 next generation and its children. But if he missed and 0:08:13.360 --> 0:08:17.520 accidentally injected the DNA into a worm's gut, nothing would happen. 0:08:18.160 --> 0:08:20.600 There wouldn't be any changes in that worm where his children. 0:08:21.080 --> 0:08:25.480 The DNA would just degrade disappear. But with r n A, 0:08:25.560 --> 0:08:28.640 Craig could inject the worm anywhere, even in the gut, 0:08:29.160 --> 0:08:31.960 and it would still have an effect. What was even 0:08:32.040 --> 0:08:35.320 stranger was that these effects were so strong and only 0:08:35.320 --> 0:08:37.760 would it last through that animal's life, but it would 0:08:37.800 --> 0:08:41.720 pass on to the next generation. Craig didn't know why 0:08:41.760 --> 0:08:45.280 that would be. All he knew is that that shouldn't 0:08:45.280 --> 0:08:49.000 be happening. He decided to call his longtime collaborator, Dr. 0:08:49.080 --> 0:08:54.240 Andrew Fire. It was very surprising, and I, of course 0:08:54.520 --> 0:08:58.120 I was very very interested in, you know, how that 0:08:58.200 --> 0:09:01.960 could be happening and it. I called up Handy and 0:09:02.000 --> 0:09:06.400 we spent hours talking about experiments. We talked about how 0:09:06.480 --> 0:09:12.720 this might what this might be. Slowly they realized what 0:09:12.760 --> 0:09:16.840 they had discovered. By tinkering with RNA instead of DNA, 0:09:17.559 --> 0:09:20.480 they could eliminate a wrong message sent by a bad 0:09:20.720 --> 0:09:24.600 DNA blueprint. It was as if the contractor never showed 0:09:24.640 --> 0:09:29.320 up for work. The faulty building never got built. Craig 0:09:29.440 --> 0:09:33.240 and doctor Fire continued to experiment and began publishing their results. 0:09:33.880 --> 0:09:35.960 In two thousand and six, they would win the Nobel 0:09:36.040 --> 0:09:40.439 Prize for discovering the phenomenon now known as RNA interference. 0:09:41.160 --> 0:09:43.960 People hoped it could usher an as dramatic a medical 0:09:44.040 --> 0:09:47.520 revolution as the insulin discovery Craig had read about in 0:09:47.559 --> 0:09:52.400 the Washington Post eight years earlier. Their work delighted scientists 0:09:52.880 --> 0:09:57.000 could researchers finally be able to treat genetic disease, but 0:09:57.080 --> 0:10:00.720 it also fired up entrepreneurs. Was their need to be made? 0:10:01.400 --> 0:10:11.720 The race was on. A research scientist named Rachel Myers 0:10:11.800 --> 0:10:15.920 answered the call back in Cambridge, Massachusetts. Rachel signed on 0:10:15.960 --> 0:10:19.600 as one of al nylum's first employees. Rachel has a 0:10:19.640 --> 0:10:23.640 near perfect scientific resume. She earned her PhD from m 0:10:23.679 --> 0:10:26.480 I T and completed a post doc at Harvard Medical School. 0:10:27.200 --> 0:10:30.040 She was working at another hot biotechnology company in town 0:10:30.080 --> 0:10:31.800 when she got the call to join a nylum in 0:10:31.840 --> 0:10:36.360 two thousand three. She stayed for fourteen years. Most of 0:10:36.400 --> 0:10:40.280 that time I spent working on one central problem, one 0:10:40.320 --> 0:10:43.560 that's pretty common in the biotech industry. How do you 0:10:43.640 --> 0:10:49.360 turn breakthrough research into something patients can actually use? Very quickly, 0:10:49.360 --> 0:10:53.200 it became clear that there was one enormous challenge, and 0:10:53.240 --> 0:10:57.440 that challenge is what we call the delivery challenge. In 0:10:57.559 --> 0:10:59.920 order to make a drug that works by this mechan 0:11:00.080 --> 0:11:02.120 is and you have to make a piece of RNA 0:11:02.520 --> 0:11:04.800 and you have to introduce it into the cells. And 0:11:05.200 --> 0:11:07.240 that sounds easy when I say it, but it turns 0:11:07.240 --> 0:11:10.960 out that's extremely difficult, and it's difficult because an RNA 0:11:11.120 --> 0:11:15.920 drug has two properties that make it very much not 0:11:16.520 --> 0:11:21.040 a good kind of medicine. And the simple properties are 0:11:21.160 --> 0:11:26.439 it's um got very high charge and it's big, very 0:11:26.520 --> 0:11:33.200 very big. So it's probably, let's see, thirty times larger 0:11:33.240 --> 0:11:35.680 than a normal drug like an aspirin that you would take, 0:11:36.600 --> 0:11:39.839 and that makes it very difficult to think about how 0:11:39.880 --> 0:11:42.600 you deliver it, get it to the places it needs 0:11:42.640 --> 0:11:45.480 to go. At what point did you realize that that 0:11:45.600 --> 0:11:48.480 was going to be the major challenge in the very beginning, 0:11:48.480 --> 0:11:52.240 and in fact, people all over the world talked about 0:11:52.320 --> 0:11:56.080 that as the challenge with developing drugs and RNA interference 0:11:56.160 --> 0:11:58.800 the delivery challenge. So you joined on nyleum knowing that 0:11:58.800 --> 0:12:01.600 that was going to be the major little If you 0:12:01.679 --> 0:12:04.480 miss some of that, like RNA having a high charge 0:12:04.520 --> 0:12:08.079 and being large, don't worry. You're not alone. You don't 0:12:08.080 --> 0:12:10.840 have to understand the details. But here's why it matters. 0:12:11.320 --> 0:12:13.960 What made r N a I so interesting in worms 0:12:14.000 --> 0:12:16.080 was that you can inject it anywhere and it worked. 0:12:16.920 --> 0:12:21.240 But that was worms. This was humans, and taking a 0:12:21.320 --> 0:12:25.400 drug from worms to humans is almost impossible. In fact, 0:12:25.440 --> 0:12:27.560 as a reporter, I'm surprised to learn that's how really 0:12:27.600 --> 0:12:29.840 the science was in two thousand two when they started. 0:12:30.640 --> 0:12:33.520 If someone pitched me today with a scientific studies saying 0:12:33.559 --> 0:12:37.200 they cured disease and worms, I would honestly think they 0:12:37.200 --> 0:12:40.520 were Charlottean trying to get one over on unsuspecting reporters 0:12:40.679 --> 0:12:49.720 or investors. Worms are easy, humans are hard. Throughout this time, 0:12:49.840 --> 0:12:52.840 Rachel and her colleagues were also thinking about another challenge, 0:12:53.480 --> 0:12:57.680 what disease should they even focus on. Drug companies must 0:12:57.760 --> 0:13:01.360 choose which diseases they attack, and maybe the most important 0:13:01.400 --> 0:13:04.760 decision they make. These decisions aren't made in a vacuum. 0:13:04.840 --> 0:13:07.920 Drugs don't work in every illness, but in this case, 0:13:08.400 --> 0:13:12.280 in theory, at least, discovery could cure perhaps an unlimited 0:13:12.440 --> 0:13:18.640 array of diseases very quickly. However, that field narrowed, so 0:13:18.679 --> 0:13:23.040 as we continue to develop the technology, we learned something 0:13:23.160 --> 0:13:28.040 really important. The delivery challenge and the solution to the 0:13:28.040 --> 0:13:32.160 delivery problem lead us to a particular tissue, a particular 0:13:32.200 --> 0:13:34.120 part of the body, and that part of the body 0:13:34.200 --> 0:13:37.640 is the liver. And that was an enormous and important 0:13:38.280 --> 0:13:42.200 finding that the best candidates we had for making drugs 0:13:42.480 --> 0:13:45.160 worked by going to the liver. And so once I 0:13:45.240 --> 0:13:47.360 tell you that, then you say, okay. So now if 0:13:47.400 --> 0:13:52.000 we think about diseases, we have to think in a 0:13:52.160 --> 0:13:55.120 somewhat refined way, right, and we have to think about 0:13:55.160 --> 0:13:59.920 diseases for which a drug going to the liver is important. 0:14:00.280 --> 0:14:04.440 So we started a very elaborate exercise to ask the question, 0:14:04.760 --> 0:14:09.280 if we look out across medicine, what are the important 0:14:09.800 --> 0:14:13.440 diseases with unmet needs where a drug going to the 0:14:13.480 --> 0:14:17.439 liver will have an impact on that disease? That exercise 0:14:17.480 --> 0:14:20.520 would eventually lead researchers to a disease whose name is 0:14:20.520 --> 0:14:25.160 a mouthful. It's a type of hereditary amyloidosis. It's a 0:14:25.200 --> 0:14:28.080 disease so rare that it often appears as a mystery 0:14:28.080 --> 0:14:31.840 illness on shows like E. Rn House, where doctors aren't 0:14:31.840 --> 0:14:36.520 a race against time to figure out a diagnosis. Doctor, 0:14:37.160 --> 0:14:47.120 you have amyloidosis. Why should I believe him? Now? Television aside, 0:14:47.200 --> 0:14:51.000 the illness is incredibly rare and incredibly tragic. My middle 0:14:51.040 --> 0:14:54.280 age patients developed something called neuropathy, a kind of tingling 0:14:54.280 --> 0:14:57.360 that begins in their toes and fingers but progressively spreads 0:14:58.120 --> 0:15:03.040 sufferers eventually can't walk, their heart deteriorates, their stomachs can't 0:15:03.040 --> 0:15:08.080 process food, and they ultimately waste away and die. The 0:15:08.160 --> 0:15:11.440 disease is genetic, meaning that it runs in families. Some 0:15:11.520 --> 0:15:14.520 people get it and some people don't, but it comes 0:15:14.520 --> 0:15:18.080 on slowly. For some people can start in their twenties. 0:15:18.320 --> 0:15:21.720 For others it starts in middle age. If it ran 0:15:21.760 --> 0:15:24.840 in my family, there was no treatment for it. I'm 0:15:24.880 --> 0:15:26.360 not sure if I would want to know if I 0:15:26.400 --> 0:15:32.000 had it or not. Back when all Nylum started researching 0:15:32.040 --> 0:15:35.280 the disease, there was no approved drug that treated the 0:15:35.360 --> 0:15:38.760 underlying condition. But all Nyleum, with its approach of altering 0:15:38.800 --> 0:15:41.200 illness at the genetic level, stood a good chance at 0:15:41.240 --> 0:15:44.720 being able to address it. But they needed money. John 0:15:44.760 --> 0:15:47.960 Marganorri is the CEO of all Nylum. He's the only 0:15:48.000 --> 0:15:50.920 CEO of the company has ever had. He's a scientist 0:15:50.960 --> 0:15:53.200 by training. He got a PhD from the University of 0:15:53.240 --> 0:15:56.520 Chicago and is the son of Greek immigrants. In a 0:15:56.560 --> 0:15:58.520 profile I read about him, I found out he liked 0:15:58.520 --> 0:16:01.120 to play pool and smokes the accase general cigar, which 0:16:01.160 --> 0:16:03.680 I can totally see. I can tell you John is 0:16:03.760 --> 0:16:07.320 ubiquitous around Cambridge. He's one of the first CEOs I've 0:16:07.360 --> 0:16:10.440 met here, and I don't think that's a coincidence. He 0:16:10.480 --> 0:16:13.320 seems to pop up everywhere. Part of that is because 0:16:13.360 --> 0:16:15.760 as the CEO of al Nylum, John has seen it 0:16:15.800 --> 0:16:19.040 all Back when he joined the company, it needed money, 0:16:19.160 --> 0:16:21.840 and lots of it. When I joined, we had raised 0:16:21.880 --> 0:16:24.320 seventeen and a half million dollars. I mean, I knew 0:16:24.320 --> 0:16:27.360 when I started that we would need to take probably 0:16:27.400 --> 0:16:30.240 a decade or more before we had our first drug 0:16:30.640 --> 0:16:32.840 that would come out of the science, and I knew 0:16:32.880 --> 0:16:35.160 that it would take billions of dollars to ultimately do it. 0:16:35.440 --> 0:16:37.640 Luckily for the company, the science was starting to get 0:16:37.680 --> 0:16:40.280 a buzz. I mean, there was a lot of early 0:16:40.320 --> 0:16:42.880 excitement around our interference. You know, it was written up 0:16:42.880 --> 0:16:45.120 in as the as the as the molecule of the 0:16:45.240 --> 0:16:48.840 Year by Science in two thousand two. You know, Forbes 0:16:48.920 --> 0:16:51.760 wrote an article about it being the next billion dollar 0:16:52.360 --> 0:16:56.320 breakthrough in biotechnology. Al Nylum started doing deals with big 0:16:56.360 --> 0:17:02.480 companies Merk, Novartis, roche To Cada. Ultimately we raised over 0:17:02.520 --> 0:17:06.280 a billion dollars from pharmaceutical partnerships that we formed. Soon 0:17:06.600 --> 0:17:08.600 urn Ai as it became known was one of the 0:17:08.600 --> 0:17:13.879 hottest areas of biotech. Everybody wanted a piece. But then 0:17:14.080 --> 0:17:18.080 something alarming started to happen. Trials that used urn Ai 0:17:18.320 --> 0:17:22.280 started to fail. Companies began to leave the field, splashy 0:17:22.280 --> 0:17:26.520 acquisitions were written off, pharmaceutical partnerships ended. It started to 0:17:26.520 --> 0:17:29.240 seem like all Nyleum might also be headed for extinction. 0:17:29.800 --> 0:17:33.119 We had many, many near death moments as a company. 0:17:33.240 --> 0:17:37.639 We had one in where basically the entirety of the 0:17:37.640 --> 0:17:41.240 pharmaceutical industry, who we're working with us earlier to help 0:17:41.280 --> 0:17:43.880 fund the company and help advance some of the science, 0:17:44.119 --> 0:17:46.879 they basically gave up hope and they left the field. 0:17:46.880 --> 0:17:50.280 And so there was a very strong vote of no confidence, 0:17:50.320 --> 0:17:52.720 if you will, in what we were doing as a 0:17:52.760 --> 0:17:55.480 public company. We were trading under our cash. We had 0:17:55.520 --> 0:17:57.960 more cash on our balance sheet than we had stock 0:17:58.040 --> 0:18:01.720 value as a stock. So that it's a pretty dire moment. 0:18:02.200 --> 0:18:06.879 I can't emphasize this enough. Biotech companies fail all the time. 0:18:07.280 --> 0:18:10.600 Clinical trial results will be disappointing, investors will figure the 0:18:10.600 --> 0:18:15.199 science doesn't work, people pick up and move on. What 0:18:15.359 --> 0:18:18.960 happens much more rarely in biotechnology is what happened next. 0:18:19.600 --> 0:18:23.120 The company stuck with it, and thanks to John's fundraising 0:18:23.240 --> 0:18:25.960 through the good times, they had the cash to actually 0:18:26.000 --> 0:18:29.679 see the science through. After sixteen years of research, On 0:18:29.720 --> 0:18:32.960 August ten of this year, on Nylum won approval for 0:18:33.040 --> 0:18:37.200 on Patro, it's first drug and the first drug ever 0:18:37.280 --> 0:18:42.440 approved to use RNA interference. John recounts the moment, Oh, 0:18:42.440 --> 0:18:45.679 that's a funny story. I was actually on a stage 0:18:46.080 --> 0:18:49.680 talking to our field force. My long standing partner and 0:18:50.280 --> 0:18:53.520 our president, Barry green Um was looking at it at 0:18:53.520 --> 0:18:57.160 his emails as he often does, and he screams out, John, 0:18:57.240 --> 0:19:01.400 we just got approved. And sure enough, you know we did. Uh. 0:19:01.440 --> 0:19:03.359 And I was there and got a round of applause 0:19:03.400 --> 0:19:06.080 from everybody. Um, Barry came up, I gave him a 0:19:06.080 --> 0:19:08.520 big hug, and you know, off we went. So it 0:19:08.560 --> 0:19:11.240 was literally couldn't have been more. It could have been 0:19:11.240 --> 0:19:14.639 better planned. It was a watershed moment, not just for 0:19:14.680 --> 0:19:18.320 the company, but for the industry. At least a dozen 0:19:18.359 --> 0:19:21.680 biotech companies are working on therapies, which, like all Nylum, 0:19:21.760 --> 0:19:25.159 seek to treat disease at the genetic level. If All 0:19:25.240 --> 0:19:27.520 Nylum could do it, the hope is that they can too. 0:19:28.640 --> 0:19:31.679 In many ways. The drug represents the best aspects of 0:19:31.720 --> 0:19:37.160 the industry, but it also represents its insane economics. An 0:19:37.160 --> 0:19:40.000 Alum's drug will cost four hundred and fifty thousand dollars 0:19:40.000 --> 0:19:43.080 a year four hundred and fifty thousand dollars a year 0:19:43.760 --> 0:19:48.080 before any discounts. Only three thousand patients with this disease 0:19:48.080 --> 0:19:51.840 have ever been diagnosed. Even at that high price, was 0:19:51.960 --> 0:19:55.359 so few patients, it's unlikely that this drug will be 0:19:55.400 --> 0:19:59.200 profitable anytime soon. It is a long time between now 0:19:59.240 --> 0:20:01.520 and being profitable as a company. We can't do it 0:20:01.560 --> 0:20:04.280 on patrol alone. We obviously have other products in our 0:20:04.320 --> 0:20:07.440 pipeline to bring forward to ultimately um, you know, get 0:20:07.480 --> 0:20:09.280 to a point as a company where we could be 0:20:09.320 --> 0:20:14.280 a sustainable business. In its first three months on the market, 0:20:14.480 --> 0:20:17.400 the drug generated only a half a million in sales, 0:20:18.080 --> 0:20:23.080 a pittance in biotech. Investors are worried. Shares declined by 0:20:23.119 --> 0:20:27.000 more than this year, but the market still sees promise. 0:20:27.560 --> 0:20:29.960 The company has a market value of more than seven 0:20:29.960 --> 0:20:33.200 billion dollars. To give you a sense, that's about the 0:20:33.240 --> 0:20:37.119 size of Dunkin Donuts or Jet Blue, companies that are profitable. 0:20:38.040 --> 0:20:41.480 Unlike all Nylum, which has generated hundreds of millions in losses. 0:20:42.640 --> 0:20:45.680 But all Nylum isn't selling coffee or cheap flights to Florida. 0:20:46.600 --> 0:20:49.320 What they do can mean the difference between life and death. 0:20:49.880 --> 0:20:54.760 It's an awesome responsibility. But what keeps me going is 0:20:54.760 --> 0:20:57.120 the fact that we know we have an important approach 0:20:57.400 --> 0:21:00.239 for new medicines, and we have an ability to make 0:21:00.280 --> 0:21:03.240 a big difference in patients lives. And you know, every 0:21:03.240 --> 0:21:05.200 morning I wake up, I'm excited to go to work, 0:21:05.840 --> 0:21:11.320 even to this day. Here's the scary truth about drug development. 0:21:11.960 --> 0:21:16.280 It can be arbitrary. Scientific breakthroughs can send billions of 0:21:16.280 --> 0:21:20.240 pharmaceutical dollars into any given field, but one high profile 0:21:20.400 --> 0:21:24.400 failure can just as easily make that money disappear. Some 0:21:24.440 --> 0:21:29.600 companies survive, but many don't. Firms get sold, research teams disperse, 0:21:30.320 --> 0:21:34.760 patients die. Most drugs never go anywhere. They sit on shelves. 0:21:35.280 --> 0:21:38.760 Small percentage going to clinical trials, and many of those fail. 0:21:39.600 --> 0:21:43.320 But every so often one makes it through. And that's 0:21:43.359 --> 0:21:56.520 only the beginning. And that's it for this week's prognosis. 0:21:56.720 --> 0:21:59.479 Thanks for listening. Do you have a story about healthcare 0:21:59.480 --> 0:22:01.720 in the US or around the world. We want to 0:22:01.760 --> 0:22:04.959 hear from you. You can email me m Cortes at 0:22:05.000 --> 0:22:08.520 Bloomberg dot net or find me on Twitter at big Cortes. 0:22:08.880 --> 0:22:11.040 If you are a fan of this episode, please take 0:22:11.080 --> 0:22:13.480 a moment to rate and review us. It helps new 0:22:13.520 --> 0:22:17.119 listeners find the show. This episode was produced by Liz Smith. 0:22:17.480 --> 0:22:20.840 Our story editor was John Heckinger. Thanks also to Drew Armstrong, 0:22:21.119 --> 0:22:24.520 Francesco Levi's head of Bloomberg Podcasts. We'll see you next week.